Paste for producing bone cement

ABSTRACT

A paste is provided from which bone cement can be formed, which is to the largest extent possible bubble-free and has a high impact strength. The paste includes (i) 15-50 weight percent of at least one mono-functional, hydrophobic methacrylic acid ester, (ii) 40-85 weight percent of at least one filler, (iii) 0.01-4 weight percent of at least one radical initiator soluble in the methacrylic acid ester (i) and having at least one peroxide group, (iv) 0.01-4 weight percent of at least one radical initiator soluble in the methacrylic acid ester (i) and having no peroxide groups, (v) 0.000001-3 weight percent of at least one accelerator soluble in the methacrylic acid ester (i) and capable of forming radicals from the radical initiators according to (iii) and (iv), (vi) 0.001-5 weight percent of at least one halide salt, and (vii) 0.2-3 weight percent of at least one cross-linking agent.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.13/012,909 filed on Jan. 25, 2011, which claims the benefit of GermanPatent Application No. 10 2010 005 956.0 filed in Germany on Jan. 27,2010, the entire contents of which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

The present invention relates to a kit for the production of bonecement, a paste for the production of bone cement, and uses of the kitand the paste.

Bone cements based on poly(methyl methacrylate) (PMMA) have been knownfor decades and trace back to the basic work done by Sir Charnley(Charnley, J., “Anchorage of the femoral head prosthesis of the shaft ofthe femur,” J. Bone Joint Surg. 42: 28-30 (1960)). In principle, thebasic configuration of the PMMA bone cements has remained the same sincethen. PMMA bone cements comprise a fluid monomer component and a powdercomponent. The monomer component includes, in general, the monomermethyl methacrylate and an activator (for example,N,N-dimethyl-p-toluidine) dissolved in this monomer. The powdercomponent comprises one or more polymers produced by polymerization,preferably suspension polymerization, based on methyl methacrylate andcomonomers, such as styrene, methyl acrylate, or similar monomers, aradiopaque material, and the initiator (for example, dibenzoylperoxide). When the powder component is mixed with the monomercomponent, due to the swelling of the polymers of the powder componentin the methyl methacrylate, a plastically deformable paste is produced.Simultaneously, the activator N,N-dimethyl-p-toluidine reacts with thedibenzoyl peroxide, which breaks down with the formation of radicals.The formed radicals initiate the radical polymerization of the methylmethacrylate. With advancing polymerization of the methyl methacrylate,the viscosity of the cement paste increases until the paste solidifiesand is thus cured.

The basic mechanical requirements on PMMA bone cements, such as 4-pointflexural strength, flexural modulus, and compression strength, aredescribed in ISO 5833. For the person applying the PMMA bone cement, theproperty of non-adhesiveness of the bone cement is of significantimportance. The term “non-adhesiveness” is defined in ISO 5833. Forconventional PMMA bone cements, non-adhesiveness indicates that thecement has reached the workable phase after the mixing of the componentsdue to the swelling of the polymers contained in the cement powder inthe monomer. Basically, a PMMA bone cement must be non-adhesive, so thatthe user can form and apply the cement. The PMMA bone cement must notadhere to gloves and application aids, such as mixing systems,crucibles, or spatulas.

The significant disadvantage of the previous PMMA bone cements for themedical user consists in that the user must mix the liquid monomercomponent with the powder component in a mixing system or in cruciblesdirectly before the application of the cement. Here, mixing errors caneasily occur, which could negatively affect the cement quality. Themixing must be performed in an uninterrupted process. Here, it isimportant that the entire cement powder be mixed with the monomercomponent without the formation of clumps and that during the mixingprocess the entry of air bubbles be avoided. With the use of vacuummixing systems, in contrast to hand mixing, the formation of air bubblesin the cement paste is largely prevented, but an additional vacuum pumpis required for these systems. Examples of mixing systems are disclosedin the publications: U.S. Pat. No. 4,015,945, European patentapplication publication EP 0 674 888 A1, and Japanese patent applicationpublication (Kokai) JP 2003/181270 A. Vacuum mixing systems and vacuumpumps are relatively expensive. After the mixing of the monomercomponent with the powder component, depending on the type of thecement, a more or less long time must elapse until the cement paste isnon-adhesive and can be applied. Due to the many possible errors in themixing of conventional PMMA bone cements, appropriately trainedpersonnel are needed. The training entails not insignificant costs.Furthermore, the mixing of the fluid monomer component with the powdercomponent leads to an exposure of the user to monomer vapors and to therelease of powdery cement particles.

In order to prevent these conditions during the production of a bonecement from a fluid monomer solution and a polymer powder, German PatentDE 10 2007 050 762 B3 proposes a paste-like bone cement. This paste-likebone cement is based on the idea of dissolving a polymer in amethacrylate monomer and suspending in this solution a particulatepolymer not soluble in the methacrylate monomer. In this way, it ispossible to produce a paste-like mass that exhibits high inner cohesiondue to the dissolved polymer and has high viscosity due to theparticulate, non-soluble polymer, so that the paste can temporarilywithstand the bleeding pressure. Due to radical polymerization of themethacrylate monomers, the paste can be cured. The radicalpolymerization is possible with (i) a radical initiator, such asbarbituric acid derivatives or dibenzoyl peroxide, and (ii) a coppersalt as the activator. It has been shown, however, that with the use ofthis initiator system, the formed bone-cement paste does not cureuniformly, but instead from the core outward in the direction of thesurface of the formed bone-cement paste. Due to the evaporation of themonomer contained in the bone-cement paste, bubbles are formed in theresulting bone cement. Furthermore, it has been observed that with theuse of this initiator system, the monomers contained in the bone-cementpaste are not completely converted. These circumstances have adisadvantageous effect on the physical properties of the bone cement, inparticular on the impact strength.

BRIEF SUMMARY OF THE INVENTION

The invention is therefore based on the object of providing a kit thatallows the production of bone cement that is bubble-free to the greatestextent possible with high impact strength. Another object consists inproviding a paste from which bone cement can be formed that isbubble-free to the greatest extent and exhibits a high impact strength.

The first object is achieved according to the invention by providing akit comprising:

a kit component (a), which contains as components at least (a1) amono-functional, hydrophobic methacrylic acid ester, (a2) a filler, and(a3) a radical initiator soluble in (a1) and having at least oneperoxide group, wherein kit component (a) contains 15-85 weight percentmethacrylic acid ester (a1) and less than 85 weight percent fillers(a2), based on the total weight of the components contained in kitcomponent (a), a kit component (b), which contains as components atleast (b1) a mono-functional, hydrophobic methacrylic acid ester, (b2) afiller, and (b3) a radical initiator soluble in (b1) and having noperoxide group, wherein kit component (b) contains 15-85 weight percentmethacrylic acid ester (b1) and less than 85 weight percent fillers(b2), based on the total weight of the components contained in kitcomponent (b),

a kit component (c), which contains as components at least (c1) amono-functional, hydrophobic methacrylic acid ester, (c2) a filler, and(c3) an accelerator soluble in (c1) and capable of forming radicals fromthe radical initiators (a3) and (b3), wherein kit component (c) contains15-85 weight percent methacrylic acid ester (c1) and less than 85 weightpercent fillers (c2), based on the total weight of the componentscontained in kit component (c),

wherein at least one of the kit components (a), (b), or (c) contains atleast one halide salt,

wherein at least one of the kit components (a), (b), or (c) contains atleast one cross-linking agent, and

wherein, based on the total weight of the components contained in thekit components (a), (b), and (c), (i) the total weight percentage of themethacrylic acid esters (a1), (b1), and (c1) lies in the range of 15-50weight percent, (ii) the total weight percentage of the fillers (a2),(b2), and (c2) lies in the range of 40-85 weight percent, (iii) theweight percentage of the radical initiator (a3) lies in the range of0.01-4 weight percent, (iv) the weight percentage of the radicalinitiator (b3) lies in the range of 0.01-4 weight percent, (v) theweight percentage of the accelerator (c3) lies in the range of0.000001-3 weight percent, (vi) the total weight percentage of the atleast one halide salt lies in the range of 0.001-5 weight percent, and(vii) the total weight percentage of the at least one cross-linkingagent lies in the range of 0.2-3 weight percent.

Furthermore, the second object is achieved according to the invention byproviding a paste comprising:

(i) 15-50 weight percent of at least one mono-functional, hydrophobicmethacrylic acid esters,

(ii) 40-85 weight percent of at least one filler,

(iii) 0.01-4 weight percent of at least one radical initiator soluble inthe methacrylic acid ester (i) and having at least one peroxide group,

(iv) 0.01-4 weight percent of at least one radical initiator soluble inthe methacrylic acid ester (i) and having no peroxide group,

(v) 0.000001-3 weight percent of at least one accelerator soluble in themethacrylic acid ester (i) and capable of forming radicals from theradical initiators according to (iii) and (iv),

(vi) 0.001-5 weight percent of at least one halide salt, and

(vii) 0.2-3 weight percent of at least one cross-linking agent.

Through the combination of the system, according to the invention, ofradical initiators that are different from each other and theaccelerator, on one hand, as well as the cross-linking agent, on theother hand, the production of a nearly bubble-free bone cement with highimpact strength, which reaches its final strength within a few minutes,is possible.

If, as known from DE 10 2007 050 762 B3, for the polymerization of themonomers contained in the bone-cement paste, either a barbituric acidderivative or a peroxide together with a copper salt is used as theinitiator, then this leads to a reduction of the impact strength due tothe formation of bubbles and incomplete conversion of the monomerscontained in the bone-cement paste.

Surprisingly, it was found that the impact strength of the bone cementcan be increased if, on one hand, an initiator system is used whichcontains at least one radical initiator having a peroxide group, aradical initiator having no peroxide group, as well as a suitableaccelerator and, on the other hand, the polymerization takes place inthe presence of a defined concentration of a cross-linking agent.

These effects are possibly traced back to the fact that, due to the useof the radical initiator having no peroxide group, it leads to a quickonset of the polymerization and a uniform heating. In connectiontherewith, solidification sets in when post-curing is initiated by theradical initiator containing at least one peroxide group. Thispost-curing is accompanied by a strong thermal shock. Furthermore, itappears to lead to a reaction between the two different radicalinitiators with the result that the polymerization process is performedcompletely. Due to the simultaneous presence of the cross-linking agent,this leads to a massive increase in viscosity setting in during an earlystage of the curing.

According to the invention, it is essential that the redox initiatorhaving at least one peroxide group is separated from the redox initiatorhaving no peroxide group before the mixing of the kit components. Ifboth redox initiators were present together in one kit component, thenthis would lead to the formation of radicals due to a reaction betweenthe two redox initiators and thus to an undesired polymerization of themonomers present, so that these kit components would not be stable forstorage. Thus, at least three kit components are required that containthe following components separate from each other: (i) a redox initiatorhaving a peroxide group, (ii) a redox initiator having no peroxidegroup, and (iii) an accelerator.

Thus, according to the invention, a kit is provided. In the scope of theinvention, a kit is understood to be a system having several separatelypackaged kit components. The individual kit components can be provided,for example, packaged in a sterile way in bottles or bags.

DETAILED DESCRIPTION OF THE INVENTION

In the present case, the kit comprises at least the three kit components(a), (b), and (c) that contain different components and thus havedifferent compositions. It is also possible according to the inventionthat the kit contain more than three kit components. By mixing thecompositions contained in the at least three kit components, initially apaste can be produced, which finally can be shaped by the user, in orderto form bone cement after the curing.

Kit component (a) contains as components at least (a1) amono-functional, hydrophobic methacrylic acid ester, (a2) a filler, and(a3) a radical initiator soluble in (a1) and having at least oneperoxide group, wherein kit component (a) contains 15-85 weight percentmethacrylic acid ester (a1) and less than 85 weight percent of thefillers (a2), based on the total weight of the components contained inkit component (a).

In addition, kit component (a) could comprise additional components. Itis also possible, however, that kit component (a) consists of thecomponents named above.

Any hydrophobic ester of methacrylic acid can be used as themono-functional, hydrophobic methacrylic acid ester (a1).

Through the use of hydrophobic, mono-functional methacrylic acid esters(a1), a later increase in volume of the bone cement and thus damage tothe bone can be prevented. According to a preferred embodiment, themono-functional methacrylic acid ester (a1) is hydrophobic, when itcontains, besides the ester group, no additional polar groups.Preferably, the mono-functional, hydrophobic methacrylic acid ester (a1)has no carboxyl groups, hydroxyl groups, amide groups, sulfonic acidgroups, sulfate groups, phosphate groups, or phosphonate groups.

The methacrylic acid esters (a1) used according to the inventionpreferably have a weight average molecular weight of less than 1000g/mol.

In the scope of the invention, data on the molecular weight refer to theviscometrically determined molecular weight.

The ester used is preferably an alkyl ester. According to a preferredembodiment, the alkyl esters are esters of methacrylic acid withalcohols having 1-20 carbon atoms, more preferred 1-10 carbon atoms,even more preferred 1-6 carbon atoms, and very especially preferred 1-4carbon atoms. The alcohols can be substituted or unsubstituted and arepreferably unsubstituted. Furthermore, the alcohols can be saturated orunsaturated and are preferably saturated.

According to an especially preferred embodiment, the mono-functional,hydrophobic methacrylic acid ester (a1) comprises methacrylic acidmethyl ester or methacrylic acid ethyl ester.

Kit component (a) contains 15-85 weight percent, preferably 20-70 weightpercent, more preferred 25-60 weight percent, and even more preferred25-50 weight percent of at least one mono-functional, hydrophobicmethacrylic acid ester (a1), based on the total weight of the componentscontained in kit component (a). Consequently, kit component (a) cancontain one or more structurally different, mono-functional, hydrophobicmethacrylic acid esters (a1), as long as the total weight of themono-functional, hydrophobic methacrylic acid esters (a1) lies in thespecified range.

The at least one filler (a2) contained in kit component (a) is amaterial that is solid at room temperature and is capable of increasingthe viscosity of the mixture composed of the other components in kitcomponent (a). The filler (a2) must be biocompatible.

According to a preferred embodiment, the filler (a2) is selected fromthe group consisting of (i) polymers soluble in at least the or one ofthe methacrylic acid esters (a1), (b1), and (c1), more preferredpolymers soluble in at least the or one of the methacrylic acid esters(a1), (ii) polymers insoluble in at least the or one of the methacrylicacid esters (a1), (b1), and (c1), more preferred polymers insoluble inat least the or one of the methacrylic acid esters (a1), (iii) inorganicsalts, (iv) inorganic oxides, (v) metals, and (vi) metal alloys. Thefiller (a2) is preferably particulate. According to an especiallypreferred embodiment, the filler (a2) has an average particle size inthe range from 10 nm-100 μm and especially preferred in the range from100 nm-10 μm. As used herein, average particle size is understood to bea range of sizes assumed by at least 90 percent of the particles.

In the scope of the invention, the term “polymers” includes bothhomopolymers and copolymers.

The polymer soluble in at least one of the methacrylic acid esters (a1),(b1), and (c1) preferably comprises a polymer having a weight averagemolecular weight of at least 150,000 g/mol. For example, the polymercould comprise a polymer or copolymer of a methacrylic acid ester.According to an especially preferred embodiment, the at least onepolymer is selected from the group consisting of polymethacrylic acidmethyl ester (PMMA), polymethacrylic acid ethyl ester (PMAA),polymethacrylic acid propyl ester (PMAP), polymethacrylic acid isopropylester, and polymethyl-co-acrylic methacrylate.

The polymer insoluble in at least one of the methacrylic acid esters(a1), (b1), and (c1) comprises, for example, polyethylene,polypropylene, or polybutadiene. The polymer insoluble in at least oneof the methacrylic acid esters (a1), (b1), and (c1) can be cross-linkedor not cross-linked.

The inorganic salt usable as filler (a2) can be a salt soluble orinsoluble in the methacrylic acid ester (a1). Preferably, the inorganicsalt comprises a salt of an element selected from the 2nd main group ofthe Periodic Table of the elements. According to a preferred embodiment,the inorganic salt is a salt of calcium, strontium, or barium. Accordingto an especially preferred embodiment, the inorganic salt is calciumsulfate, barium sulfate, or calcium carbonate.

The inorganic oxide usable as filler (a2) can preferably be a metaloxide. According to a preferred embodiment, the inorganic oxide is anoxide of the transition metals. According to an especially preferredembodiment, the inorganic oxide comprises titanium dioxide or zirconiumdioxide.

The metal usable as filler (a2) can comprise, for example, a transitionmetal. According to a preferred embodiment, the metal is tantalum ortungsten.

The metal alloy usable as filler (a2) is an alloy of at least twometals. Preferably, the alloy contains at least one transition metal.According to an especially preferred embodiment, the alloy contains atleast tantalum or tungsten. The alloy could also comprise an alloy madeof tantalum or tungsten.

The percentage of the at least one filler (a2) equals less than 85weight percent, preferably less than 80 weight percent, and morepreferred less than 75 weight percent, based on the total weight of thecomponents contained in kit component (a). Preferably, kit component (a)contains 15-84.99 weight percent, more preferred 15-80 weight percent,and even more preferred 20-75 weight percent of the at least one filler(a2), based on the total weight of the components contained in kitcomponent (a). Accordingly, component (a) can contain one or morestructurally different fillers (a2) as long as the total weight of thefillers (a2) lies in the specified range.

Component (a) also contains a radical initiator (a3) soluble in themono-functional, hydrophobic methacrylic acid ester (a1) and having atleast one peroxide group. Although used in singular form here, accordingto the invention the term “radical initiator (a3)” also extends to aplurality of structurally different radical initiators (a3).

As used herein, radical initiator (a3) is understood to be a compoundfrom which a radical can be formed by the action of the accelerator(c3), wherein this radical is capable of triggering the polymerizationof the methacrylic acid ester (a1), (a2), and (a3). The radicalinitiator (a3) thus comprises a radical polymerization starter.

In the presence of the accelerator (c3), the radical initiator (a3) hasa decomposition rate different from the radical initiator (b3).According to an especially preferred embodiment, in the presence of theaccelerator (c3), the radical initiator (a3) has a lower decompositionrate than the radical initiator (b3).

According to a preferred embodiment, the solubility of the radicalinitiator (a3) in the methacrylic acid ester (a1) equals at least 0.5weight percent, based on the weight of the methacrylic acid ester (a1).

According to an especially preferred embodiment, the radical initiator(a3) is selected from the group consisting of dibenzoyl peroxide anddilauroyl peroxide.

Component (a) contains preferably 0.01-12 weight percent, preferably0.01-10 weight percent, more preferred 0.05-8 weight percent, and evenmore preferred 0.05-5 weight percent of at least one radical initiator(a3), based on the total weight of the components contained in kitcomponent (a).

Kit component (b) contains as components at least (b1) amono-functional, hydrophobic methacrylic acid ester, (b2) a filler, and(b3) a radical initiator soluble in (b1) and having no peroxide group,wherein kit component (b) contains 15-85 weight percent methacrylic acidesters (b1) and less than 85 weight percent of filler (b2), based on thetotal weight of the components contained in kit component (b). Inaddition, component (b) can comprise additional components. However, itis also possible that component (b) consists of the components mentionedabove.

Any hydrophobic ester of methacrylic acid can be used as themono-functional, hydrophobic methacrylic acid ester (b1).

Through the use of hydrophobic, mono-functional methacrylic acid esters(b1), a later increase in volume of the bone cement and thus damage tothe bone can be prevented. According to a preferred embodiment, themono-functional methacrylic acid ester (b1) is hydrophobic, if it has,in addition to the ester group, no other polar groups. Preferably, themono-functional, hydrophobic methacrylic acid ester (b1) contains nocarboxyl groups, hydroxyl groups, amide groups, sulfonic acid groups,sulfate groups, phosphate groups, or phosphonate groups.

The methacrylic acid esters (b1) used according to the inventionpreferably have a weight average molecular weight of less than 1000g/mol.

The esters preferably comprise alkyl esters. According to a preferredembodiment, the alkyl esters are esters of methacrylic acid withalcohols having 1-20 carbon atoms, more preferred 1-10 carbon atoms,even more preferred 1-6 carbon atoms, and very especially preferred 1-4carbon atoms. The alcohols can be substituted or unsubstituted and arepreferably unsubstituted. The alcohols can further be saturated orunsaturated and are preferably saturated.

According to an especially preferred embodiment, the mono-functional,hydrophobic methacrylic acid ester (b1) comprises methacrylic acidmethyl ester or methacrylic acid ethyl ester.

Kit component (b) contains 15-85 weight percent, preferably 20-70 weightpercent, more preferred 25-60 weight percent, and even more preferred25-50 weight percent of at least one mono-functional, hydrophobicmethacrylic acid ester (b1), based on the total weight of the componentscontained in kit component (b). Accordingly, kit component (b) cancontain one or more structurally different mono-functional, hydrophobicmethacrylic acid esters (b1) as long as the total weight of themono-functional, hydrophobic methacrylic acid ester (b1) lies in thespecified range.

The at least one filler (b2) contained in kit component (b) comprises amaterial that is solid at room temperature and is capable of increasingthe viscosity of the mixture composed of the other components containedin kit component (b). The filler (b2) must be biocompatible.

According to a preferred embodiment, the filler (b2) is selected fromthe group consisting of (i) polymers soluble in at least the or one ofthe methacrylic acid esters (a1), (b1), and (c1), more preferredpolymers soluble in at least the or one of the methacrylic acid esters(b1), (ii) polymers insoluble in at least the or one of the methacrylicacid esters (a1), (b1), and (c1), more preferred polymers insoluble inat least the or one of the methacrylic acid esters (b1), (iii) inorganicsalts, (iv) inorganic oxides, (v) metals, and (vi) metal alloys.

The polymer soluble in at least one of the methacrylic acid esters (a1),(b1), and (c1) preferably comprises a polymer having a weight averagemolecular weight of at least 150,000 g/mol. For example, the polymer cancomprise a polymer or copolymer of a methacrylic acid ester. Accordingto an especially preferred embodiment, the at least one polymer isselected from the group consisting of polymethacrylic acid methyl ester(PMMA), polymethacrylic acid ethyl ester (PMAA), polymethacrylic acidpropyl ester (PMAP), polymethacrylic acid isopropyl ester, andpolymethyl-co-acrylic methacrylate.

The polymer insoluble in at least one of the methacrylic acid esters(a1), (b1), and (c1) comprises, for example, polyethylene,polypropylene, or polybutadiene. The polymer insoluble in at least oneof the methacrylic acid esters (a1), (b1), and (c1) can be cross-linkedor not cross-linked.

The inorganic salt usable as filler (b2) can be a salt soluble orinsoluble in the methacrylic acid ester (b1). Preferably, the inorganicsalt comprises a salt of an element selected from the 2nd main group ofthe periodic table of the elements. According to a preferred embodiment,the inorganic salt is a salt of calcium, strontium, or barium. Accordingto an especially preferred embodiment, the inorganic salt is calciumsulfate, barium sulfate, or calcium carbonate.

The inorganic oxide usable as filler (b2) can preferably comprise ametal oxide. According to a preferred embodiment, the inorganic oxide isan oxide of the transition metals. According to an especially preferredembodiment, the inorganic oxide comprises titanium oxide or zirconiumdioxide.

The metal usable as filler (b2) can comprise, for example, a transitionmetal. According to a preferred embodiment, the metal is tantalum ortungsten.

The metal alloy usable as filler (b2) is an alloy of at least twometals. Preferably, the alloy contains at least one transition metal.According to an especially preferred embodiment, the alloy contains atleast tantalum or tungsten. The alloy can also comprise an alloy made oftantalum and tungsten.

The percentage of the at least one filler (b2) equals less than 85weight percent, preferably less than 80 weight percent, and morepreferred less than 75 weight percent, based on the total weight of thecomponents contained in kit component (b). Preferably, kit component (b)contains 15-84.99 weight percent, more preferred 15-80 weight percent,and even more preferred 20-75 weight percent of the at least one filler(b2), based on the total weight of the components contained in kitcomponent (b). Accordingly, component (b) can contain one or morestructurally different fillers (b2), as long as the total weight of thefillers (b2) lies in the specified range.

Component (b) also contains a radical initiator (b3) soluble in themono-functional, hydrophobic methacrylic acid ester (b1) and has noperoxide group. Although used here in the singular form, according tothe invention the term “radical Initiator (b3)” also extends to aplurality of structurally different radical initiators (b3).

As used herein, radical initiator (b3) is understood to be a compoundfrom which a radical can be formed by action of the accelerator (c3),wherein this compound is capable of triggering the polymerization of themethacrylic acid esters (b1), (b2), and (b3). The radical initiator (b3)thus comprises a radical polymerization starter.

In the presence of the accelerator (c3), the radical initiator (b3) hasa decomposition rate that is different from the radical initiator (a3).According to an especially preferred embodiment, in the presence of theaccelerator (c3), the radical initiator (b3) has a higher decompositionrate than the radical initiator (a3).

According to a preferred embodiment, the solubility of the radicalinitiator (b3) in the methacrylic acid ester (b1) equals at least 0.5weight percent, based on the weight of the methacrylic acid ester (b1).

The radical initiator (b3) preferably comprises barbituric acid orbarbituric acid derivatives, in which the barbituric acid carries asubstitute on at least one of the positions 1 or 5. Such barbituric acidderivatives have the advantage that they exhibit no pharmacologicalaction.

According to the invention, the barbituric acid derivative is preferablymono-substituted. According to a preferred embodiment, a barbituric acidsubstituted at position 5 is used as the radical initiator (b3). Thesubstituent of the barbituric acid derivatives furthermore preferablycomprises a hydrophobic substituent. Preferably, the barbituric acidderivative comprises an alkyl, cycloalkyl, or aryl derivative of thebarbituric acid.

According to an especially preferred embodiment, the barbituric acidderivative is selected from the group consisting of cyclohexylbarbituric acid, 1,3,5-trimethyl barbituric acid, 1-phenyl-5-benzylbarbituric acid, 1-benzyl-5-phenyl barbituric acid, 1,3-dimethylbarbituric acid, 1,3-dimethyl-5-phenyl barbituric acid,1-cyclohexyl-5-ethyl barbituric acid, 5-lauryl barbituric acid,1-n-butyl-barbituric acid, 5-n-butyl barbituric acid, 5-allyl barbituricacid, 5-hydroxy-5-butyl barbituric acid, 5,5-dibromo barbituric acid,trichloro barbituric acid, 5-nitro barbituric acid, 5-amino barbituricacid, 5-hydroxy barbituric acid, and 5,5-dihydroxy barbituric acid.

Under a very especially preferred embodiment, the barbituric acidderivative is selected from the group consisting of1-cyclohexyl-5-ethyl-barbituric acid, 1-n-butyl-barbituric acid, and5-n-butyl-barbituric acid.

According to the invention, the term “barbituric acid derivatives” alsoincludes alkaline earth salts and alkali salts of these barbituric acidderivatives.

Kit component (b) preferably contains 0.01-12 weight percent, preferably0.01-8 weight percent, more preferred 0.05-6 weight percent, and evenmore preferred 0.05-5 weight percent of at least one radical initiator(b3), based on the total weight of the components contained in kitcomponent (b). Accordingly, kit component (b) can contain one or morestructurally different radical initiators (b3), as long as the totalweight of the radical initiator (b3) lies in the specified range.

Kit component (b) [sic (c)] contains as components at least (c1) amono-functional, hydrophobic methacrylic acid ester, (c2) a filler, and(c3) an accelerator soluble in (c1) and is capable of forming radicalsfrom the radical initiators (a3) and (b3), wherein kit component (c) has15-85 weight percent methacrylic acid ester (c1), and less than 85weight percent of filler (c2) based on the total weight of thecomponents contained in kit component (c).

Any hydrophobic esters of methacrylic acid can be used as themono-functional, hydrophobic methacrylic acid ester (c1).

Through the use of hydrophobic, mono-functional methacrylic acid esters(c1), a later increase in volume of the bone cement and thus damage tothe bone can be prevented. According to a preferred embodiment, themono-functional methacrylic acid ester (c1) is hydrophobic, if it has,besides the ester group, no other polar groups. Preferably themono-functional, hydrophobic methacrylic acid ester (c1) has no carboxylgroups, hydroxyl groups, amide groups, sulfonic acid groups, sulfategroups, phosphate groups, or phosphonate groups.

The methacrylic acid esters (c1) used according to the inventionpreferably have a weight average molecular weight of less than 1000g/mol.

The esters preferably comprise alkyl esters. According to a preferredembodiment, the alkyl esters are esters of methacrylic acid withalcohols having 1-20 carbon atoms, more preferred 1-10 carbon atoms,even more preferred 1-6 carbon atoms, and very especially preferred 1-4carbon atoms. The alcohols can be substituted or unsubstituted and arepreferably unsubstituted. The alcohols furthermore can be saturated orunsaturated and are preferably saturated.

According to an especially preferred embodiment, the mono-functional,hydrophobic methacrylic acid ester (c1) comprises methacrylic acidmethyl ester or methacrylic acid ethyl ester.

Kit component (c) contains 15-85 weight percent, preferably 20-70 weightpercent, more preferred 25-60 weight percent, and even more preferred25-50 weight percent of at least one mono-functional, hydrophobicmethacrylic acid ester (c1), based on the total weight of the componentscontained in kit component (c). Accordingly, kit component (c) cancontain one or more structurally different, mono-functional, hydrophobicmethacrylic acid esters (c1), as long as the total weight of themono-functional, hydrophobic methacrylic acid esters (c1) lies in thespecified range.

The at least one filler (c2) contained in kit component (c) comprises amaterial that is solid at room temperature and is capable of increasingthe viscosity of the mixture composed of the other components containedin kit component (c). The filler (c2) must be biocompatible.

According to a preferred embodiment, the filler (c2) is selected fromthe group consisting of (i) polymers soluble in at least the or one ofthe methacrylic acid esters (a1), (b1), and (c1), more preferredpolymers soluble in at least the or one of the methacrylic acid esters(1), (ii) polymers insoluble in at least the or one of the methacrylicacid esters (a1), (b1), and (c1), more preferred polymers insoluble inat least the or one of the methacrylic acid esters (c1), (iii) inorganicsalts, (iv) inorganic oxides, (v) metals, and (vi) metal alloys.

The polymer soluble in at least one of the methacrylic acid esters (a1),(b1), and (c1) preferably comprises a polymer having a weight averagemolecular weight of at least 150,000 g/mol. For example, the polymer cancomprise a polymer or copolymer of a methacrylic acid ester. Accordingto an especially preferred embodiment, the at least one polymer isselected from the group consisting of polymethacrylic acid methyl ester(PMMA), polymethacrylic acid ethyl ester (PMAA), polymethacrylic acidpropyl ester (PMAP), polymethacrylic acid isopropyl ester, andpolymethyl-co-acrylic methacrylate.

The polymer insoluble in at least one of the methacrylic acid esters(a1), (b1), and (c1) comprises, for example, polyethylene,polypropylene, or polybutadiene. The polymer insoluble in at least oneof the methacrylic acid esters (a1), (b1), and (c1) can be cross-linkedor not cross-linked.

The inorganic salt usable as filler (c2) can be a salt soluble orinsoluble in the methacrylic acid ester (c1). Preferably the inorganicsalt comprises a salt of an element selected from the 2nd main group ofthe periodic table of the elements. According to a preferred embodiment,the inorganic salt is a salt of calcium, strontium, or barium. Accordingto an especially preferred embodiment, the inorganic salt is calciumsulfate, barium sulfate, or calcium carbonate.

The inorganic oxide usable as filler (c2) preferably can comprise ametal oxide. According to a preferred embodiment, the inorganic oxide isan oxide of the transition metals. According to an especially preferredembodiment, the inorganic oxide comprises titanium dioxide or zirconiumdioxide.

The metal usable as filler (c2) can comprise, for example, a transitionmetal. According to a preferred embodiment, the metal is tantalum ortungsten.

The metal alloy usable as filler (c2) is an alloy of at least twometals. Preferably, the alloy contains at least one transition metal.According to an especially preferred embodiment, the alloy contains atleast tantalum or tungsten. The alloy can also comprise an alloy made oftantalum and tungsten.

The percentage of the at least one filler (c2) equals less than 85weight percent, preferably less than 80 weight percent, and morepreferred less than 75 weight percent, based on the total weight of thecomponents contained in kit component (c). Preferably, kit component (c)contains 15-84.99 weight percent, more preferred 15-80 weight percent,and even more preferred 20-75 weight percent of the at least one filler(c2), based on the total weight of the components contained in kitcomponent (c). Accordingly, component (c) can contain one or morestructurally different fillers (c2), as long as the total weight of thefillers (c2) lies in the specified range.

Kit component (c) also contains an accelerator (c3) soluble in themono-functional, hydrophobic methacrylic acid ester (c1) and is capableof forming radicals from the radical initiators (a3) and (b3). Althoughused here in singular form, according to the invention the term“accelerator (c3)” also extends to a plurality of structurally differentaccelerators (c3).

According to a preferred embodiment, the solubility of the accelerator(c3) in the methacrylic acid ester (c1) equals at least 0.5 weightpercent, based on the weight of the methacrylic acid ester (c1).

According to the invention, accelerators capable of forming radicalsfrom the radical initiators (a3) and (b3) are understood to be compoundsthat can convert the radical initiators (a3) and (b3) to radicals,optionally in the presence of additional compounds contained in the kitaccording to the invention, as for example halide ions. Suchaccelerators are well known from the prior art.

The accelerator (c3) preferably comprises a salt having ions of metalsthat can assume, besides the oxidation stage 0, at least two additionaloxidation stages. According to an especially preferred embodiment, themetal ions are selected from the group consisting of copper ions, ironions, cobalt ions, and manganese ions. Accordingly, an iron salt, acobalt salt, or a manganese salt is used as the accelerator (c3).According to one very especially preferred embodiment, the accelerator(c3) is selected from the group consisting ofcopper(II)-2-ethylhexanoate, copper(II)-laurate, copper(II)-decanoate,copper(II)-octoate, copper(II) acetylacetonate, andcopper(II)-methacrylate.

Kit component (c) preferably contains 0.00001-12 weight percent,preferably 0.0001-9 weight percent, more preferred 0.001-6 weightpercent, and even more preferred 0.05-5 weight percent of at least oneaccelerator (c3), based on the total weight of the components containedin kit component (c). Accordingly, kit component (c) can contain one ormore structurally different accelerators (c3), as long as the totalweight of the accelerator (c3) lies in the specified range.

At least one of the kit components (a), (b), or (c) further contains ahalide salt. The halide salt preferably comprises a halide salt solublein at least one of the methacrylic acid esters (a1), (b1), and (c1).Preferably, the halide salt is soluble in at least one of themethacrylic acid esters (a1), (b1), and (c1), with which the halide saltis present together in the kit component.

According to a preferred embodiment, the solubility of the halide saltin at least one of the methacrylic acid esters (a1), (b1), and (c1)equals at least 0.5 weight percent, based on the weight of the at leastone methacrylic acid ester (a1), (b1), and (c1).

According to the invention, halide salts are understood to be salts thatcontain at least one type of halide ion and dissociate in at least oneof the methacrylic acid esters (a1), (b1), and (c1). Preferably, thehalide ions comprise chloride ions or bromide ions, very preferredchloride ions. According to the invention, preferably metal halides,hydrochlorides, and quaternary ammonium halide salts can be used as thehalide salts.

According to an especially preferred embodiment, the halide salt isselected from the group consisting of copper(II)-chloride,copper(II)-bromide, iron(III)-chloride, iron(III)-bromide,cobalt(II)-chloride, cobalt(II)-bromide, triethylamine hydrochloride,triethylamine hydrobromide, propylamine hydrochloride, butylaminehydrochloride, methacryloyl choline chloride, methyltrioctylammoniumchloride, and triethyl benzyl ammonium chloride.

The percentage of the at least one halide salt in at least one of thekit components (a), (b), or (c) preferably equals 0.002-10 weightpercent, preferably 0.002-7 weight percent, and more preferred 0.003-6weight percent, based on the total weight of the components contained inthis at least one kit component.

Furthermore, at least one of the kit components (a), (b), or (c)contains a cross-linking agent. The cross-linking agent comprises abi-functional or tri-functional compound. According to the invention,the cross-linking agent should cause a cross-linking of thepolymerizing, mono-functional, hydrophobic methacrylic acid ester duringthe curing of the bone cement.

According to a preferred embodiment, the cross-linking agent has atleast two acrylate groups. Especially preferred, the cross-linking agentis selected from the group consisting of ethylene glycol dimethacrylate,butylene glycol dimethacrylate (e.g., butane-1,4-diol-dimethacrylate),and hexamethylene dimethacrylate (e.g., hexane-1,6-diol-dimethacrylate).

The percentage of the at least one cross-linking agent preferably equals0.3-10 weight percent, preferably 0.4-8 weight percent, and morepreferred 0.5-6 weight percent, based on the total weight of thecomponents contained in this at least one kit component.

The kit according to the invention can furthermore contain at least onepharmaceutical substance. The pharmaceutical substance can preferably beselected from the group consisting of antibiotics, anti-inflammatoryagents, hormones, growth factors, bisphosphonates, and cytostaticagents.

The at least one antibiotic is preferably selected from the groupconsisting of gentamicin sulfate, gentamicin hydrochloride, amikacinsulfate, amikacin hydrochloride, tobramycin sulfate, tobramycinhydrochloride, clindamycin hydrochloride, lincosamine hydrochloride,moxifloxacin, ciprofloxacin, teicoplanin, vancomycin, ramoplanin,metronidazole, tinidazole, and omidazole.

The at least one anti-inflammatory agent is preferably selected from thegroup consisting of non-steroidal anti-inflammatory agents andglucocorticoids. According to an especially preferred embodiment, the atleast one anti-inflammatory agent is selected from the group consistingof acetylsalicylic acid, ibuprofen, diclofenac, ketoprofen,dexamethasone, prednisone, hydrocortisone, hydrocortisone acetate, andfluticasone.

The at least one hormone is preferably selected from the groupconsisting of serotonin, somatotropin, testosterone, and estrogen.

The at least one growth factor is preferably selected from the groupconsisting of the Fibroblast Growth Factor (FGF), Transforming GrowthFactor (TGF), Platelet Derived Growth Factor (PDGF), epidermal growthfactor (EGF), Vascular Endothelial Growth Factor (VEGF), insulin-likegrowth factors (IGF), Hepatocyte Growth Factor (HGF), interleukin-1B,interleukin 8, and nerve growth factor.

The at least one cytostatic agent is preferably selected from the groupconsisting of alkylating agents, platinum analogs, intercalating agents,mitotic inhibitors, taxanes, topoisomerase inhibitors, andantimetabolites.

The at least one bisphosphonate is preferably selected from the groupconsisting of zoledronate and aledronate.

The at least one pharmaceutical substance can be contained in one ormore of the kit components (a), (b), and (c).

According to the invention, the kit can further have a radiopaquematerial. The radiopaque material is preferably selected from the groupconsisting of zirconium dioxide, barium sulfate, and tantalum. The atleast one radiopaque material can be contained in one or more of the kitcomponents (a), (b), and (c).

According to the invention, the kit can further contain at least onedye. Especially preferred, the dye can comprise a food coloring.According to an especially preferred embodiment, chlorophyllin (E141),riboflavin, and/or lissamine green is used as the dye. The at least onedye can be contained in one or more of the kit components (a), (b), and(c).

The kit can also contain at least one stabilizer. The stabilizer shouldbe suitable for preventing spontaneous polymerization of the monomerscontained in the kit components (a), (b), and (c). Furthermore, thestabilizer should exhibit no disruptive interactions with the othercomponents contained in the kit components. Such stabilizers are knownfrom the prior art. According to a preferred embodiment, the stabilizercomprises 2,6-di-tert-butyl-4-methylphenol and/or2,6-di-tert-butyl-phenol.

The at least one stabilizer can be contained in one or more of the kitcomponents (a), (b), and (c) and is preferably contained in each of thethree kit components (a), (b), and (c).

In addition, the kit can optionally have additional additives.

Due to the defined weight percentages of methacrylic acid esters (a1),(b1), and (c1) and fillers (a2), (b2), and (c2), the kit components (a),(b), and (c) exist as pastes. This has the advantage that a bone-cementpaste can be produced by the user without a problem by mixing thedifferent paste-like kit components. In particular, the disadvantagesthat arise during the mixing of components that exist in differentaggregate states, for example, during the mixing of a powdery componentand a fluid monomer component, are eliminated.

The kit components (a), (b), and (c) are adjusted to each other so thatthe individual components contained therein are present in preciselydefined quantity ranges based on the total weight of the componentscontained in the kit components. According to the invention, totalweight of the components contained in the kit components (a), (b), and(c) is understood to be the sum of the weights of the componentscontained in the kit components (a), (b), and (c).

According to the invention, the total weight percentage of a certaincomponent, based on the total weight of the components contained in thekit components (a), (b), and (c), is understood to be the percentage ofthe total weight of the components contained in the kit components (a),(b), and (c) that is assumed by the sum of the weight percentages of thecertain component contained in the kit components (a), (b), and/or (c).

If, for example, the total weight of the components of kit component (a)add up to 100 g, the total weight of the components of kit component (b)add up to 100 g, and the total weight of the components of kit component(c) add up to 100 g, then the total weight of the components containedin the kit components (a), (b), and (c) equals 300 g.

According to this example, if 30 g of filler (a2) is contained in kitcomponent (a), 80 g of filler (b2) in kit component (b), and 40 g offiller (c2) in kit component (c), then the total weight of the fillers(a2), (b2), and (c2) equals 150 g. Accordingly, the total weightpercentage of the fillers (a2), (b2), and (c2) in this example equals 50weight percent, based on the total weight of the components contained inthe kit components (a), (b), and (c).

The total weight percentage of the methacrylic acid esters (a1), (b1),and (c1) lies in the range of 15-50 weight percent, preferably 15-45weight percent, and more preferred 20-45 weight percent, based on thetotal weight of the components contained in the kit components,preferably the kit components (a), (b), and (c).

The total weight percentage of the fillers (a2), (b2), and (c2) lies inthe range of 40-85 weight percent, preferably 42-83 weight percent, morepreferred 45-80 weight percent, and even more preferred 50-75 weightpercent, based on the total weight of the components contained in thekit components, preferably the kit components (a), (b), and (c).

Due to this percentage of methacrylic acid esters (a1), (b1), and (c1),and fillers (a2), (b2), and (c2), after mixing of the components (a),(b), and (c), a paste is produced that is easy to work by the user, inparticular easily shapeable.

The weight percentage of the radical initiator (a3) lies in the range of0.01-4 weight percent, preferably in the range of 0.01-3 weight percent,more preferred in the range of 0.05-2.5 weight percent, and even morepreferred in the range of 0.05-2 weight percent, based on the totalweight of the components contained in the kit components, preferably thekit components (a), (b), and (c).

The weight percentage of the radical initiator (b3) lies in the range of0.01-4 weight percent, preferably in the range of 0.01-3 weight percent,more preferred in the range of 0.05-2.5 weight percent, and even morepreferred in the range of 0.05-2 weight percent, based on the totalweight of the components contained in the kit components, preferably thekit components (a), (b), and (c).

The weight percentage of the accelerator (c3) lies in the range of0.00001-4 weight percent, preferably 0.0001-3 weight percent, morepreferred 0.001-3 weight percent, and even more preferred 0.05-2 weightpercent, based on the total weight of the components contained in thekit components, preferably the kit components (a), (b), and (c).

The weight percentages of the radical initiator (a3), radical initiator(b3), and accelerator (c3) are not particularly critical. A content thatis lower than the lower limits of the specified ranges leads to theresult that the curing of the bone cement takes place more slowlywithout the use of additional polymerization aids. A content that ishigher than the upper limits of the specified ranges leads to highercosts without significant added value.

The total weight percentage of the at least one halide salt lies in therange of 0.001-5 weight percent, preferably 0.005-4 weight percent, andmore preferred 0.01-4 weight percent, based on the total weight of thecomponents contained in the kit components, preferably the kitcomponents (a), (b), and (c). A minimum content of halide salts of 0.001weight percent, based on the total weight of the components contained inthe kit components is required, so that the polymerization can be set inmotion. A content of more than 5 weight percent, however, based on thetotal weight of the components contained in the kit components, hasproven disadvantageous due to the toxicity of the halides.

The total weight of the at least one cross-linking agent lies in therange of 0.2-3 weight percent, preferably 0.5-2.75 weight percent, andeven more preferred 1-2.5 weight percent, based on the total weight ofthe components (a), (b), and (c). The percentage of cross-linking agentsin this range is essential, in order to impart a high impact strength tothe cured bone cement. It has been shown that the impact strength of thecured bone cement is significantly reduced with a content of less than0.2 weight percent and greater than 3 weight percent, each based on thetotal weight of the components contained in the kit components.

According to a preferred embodiment, the percentage of the compositioncontained in kit component (a) equals 20-40 weight percent, thepercentage of the composition contained in kit component (b) equals20-40 weight percent, and the percentage of the composition contained inkit component (c) equals 20-40 weight percent, based on the total weightof the compounds contained in kit components (a), (b), and (c).

According to the invention, the kit that contains at least the kitcomponents (a), (b), and (c) is used for the production of bone cement.For this purpose, the at least three kit components (a), (b), and (c)are mixed with each other under formation of a paste. The mixture ratiopreferably equals 0.5-1.5 weight parts of kit component (a), 0.5-1.5weight parts of kit component (b), and 0.5-1.5 weight parts of kitcomponent (c).

The mixing can be carried out with typical mixing devices, for example,a static mixer or a dynamic mixer.

After the mixing of the components of the kit, the resulting paste isadhesive-free according to the ISO 5833 standard and can be immediatelyworked.

The paste can be used, for example, for fixing joint endoprostheses orfor filling bone defects. Both uses are known from the prior art inconnection with conventional pastes.

The bone cement produced from the paste through curing attains its finalstrength approximately six to eight minutes after the mixing of theindividual kit components.

The paste according to the invention contains at least onemono-functional, hydrophobic methacrylic acid ester (i). Any hydrophobicesters of the methacrylic acid can be used as the mono-functional,hydrophobic methacrylic acid ester (i).

Through the use of hydrophobic, mono-functional methacrylic acid esters(i), a later increase in volume of the bone cement and thus damage tothe bone can be prevented. According to a preferred embodiment, themono-functional methacrylic acid ester (i) is hydrophobic, if it has,besides the ester group, no additional polar groups. Preferably, themono-functional, hydrophobic methacrylic acid ester (i) has no carboxylgroups, hydroxyl groups, amide groups, sulfonic acid groups, sulfategroups, phosphate groups, or phosphonate groups.

The methacrylic acid esters (i) used according to the inventionpreferably have a weight average molecular weight of less than 1000g/mol.

The esters preferably comprise alkyl esters. According to a preferredembodiment, the alkyl esters are esters of methacrylic acid withalcohols having 1-20 carbon atoms, more preferred 1-10 carbon atoms,even more preferred 1-6 carbon atoms, and very especially preferred 1-4carbon atoms. The alcohols can be substituted or unsubstituted and arepreferably unsubstituted. The alcohols furthermore can be saturated orunsaturated and are preferably saturated. According to an especiallypreferred embodiment, the mono-functional, hydrophobic methacrylic acidester (i) comprises methacrylic acid methyl ester or methacrylic acidethyl ester.

Component (i) contains 15-50 weight percent, preferably 15-45 weightpercent, and even more preferred 20-45 weight percent of at least onemono-functional, hydrophobic methacrylic acid esters (i) based on thetotal weight of the paste. Accordingly, the paste can contain one ormore structurally different, mono-functional, hydrophobic methacrylicacid esters (i), as long as the total weight of the mono-functional,hydrophobic methacrylic acid esters (i) lies in the specified range.

According to the invention, the paste contains a filler (ii). The atleast one filler (ii) contained in the paste comprises a material thatis solid at room temperature and is capable of increasing the viscosityof the paste. The filler (ii) must be biocompatible.

According to a preferred embodiment, the filler (ii) is selected fromthe group consisting of (a) polymers soluble in at least the or one ofthe methacrylic acid esters (i), (b) polymers insoluble in at least theor one of the methacrylic acid esters (i), (c) inorganic salts, (d)inorganic oxides, (e) metals, and (f) metal alloys.

The polymer soluble in at least one of the methacrylic acid esters (i)preferably comprises a polymer having a weight average molecular weightof at least 150,000 g/mol. For example, the polymer can comprise apolymer or copolymer of a methacrylic acid ester. According to anespecially preferred embodiment, the at least one polymer is selectedfrom the group consisting of polymethacrylic acid methyl ester (PMMA),polymethacrylic acid ethyl ester (PMAA), polymethacrylic acid propylester (PMAP), polymethacrylic acid isopropyl ester, andpolymethyl-co-acrylic methacrylate.

The polymer insoluble in at least one of the methacrylic acid esters (i)comprises, for example, polyethylene, polypropylene, or polybutadiene.The polymer soluble in at least one of the methacrylic acid esters (i)can be cross-linked or not cross-linked.

The inorganic salt usable as filler (ii) can be a salt soluble orinsoluble in the methacrylic acid ester (i). Preferably, the inorganicsalt comprises a salt of an element selected from the 2nd main group ofthe periodic table of the elements. According to a preferred embodiment,the inorganic salt is a salt of calcium, strontium, or barium. Accordingto an especially preferred embodiment, the inorganic salt is calciumsulfate, barium sulfate, or calcium carbonate.

The inorganic oxide usable as filler (ii) can preferably comprise ametal oxide. According to a preferred embodiment, the inorganic oxide isan oxide of the transition metals. According to an especially preferredembodiment, the inorganic oxide comprises titanium dioxide or zirconiumdioxide.

The metal usable as filler (ii) can comprise, for example, a transitionmetal. According to a preferred embodiment, the metal is tantalum ortungsten.

The metal alloy usable as filler (ii) is an alloy of at least twometals. Preferably, the alloy contains at least one transition metal.According to an especially preferred embodiment, the alloy contains atleast tantalum or tungsten. The alloy can also comprise an alloy made oftantalum and tungsten.

The percentage of the at least one filler (ii) equals 40-85 weightpercent, preferably 40-80 weight percent, and more preferred 45-75weight percent, based on the total weight of the paste. Accordingly, thepaste can contain one or more structurally different fillers (ii), aslong as the total weight of the fillers (ii) lies in the specifiedrange.

The paste further contains at least one radical initiator (iii) solublein the at least one mono-functional, hydrophobic methacrylic acid ester(i) and has at least one peroxide group. As used herein, a radicalinitiator (iii) is understood to be a compound from which a radical canbe formed by the action of the accelerator (v), wherein this radical iscapable of triggering the polymerization of the at least one methacrylicacid ester (i). The radical initiator (iii) thus comprises a radicalpolymerization starter.

In the presence of the accelerator (v), the at least one radicalinitiator (iii) has a decomposition rate that is different from theradical initiator (iv). According to an especially preferred embodiment,in the presence of the accelerator (v), the radical initiator (iii) hasa lower decomposition rate than the radical initiator (iv).

According to a preferred embodiment, the solubility of the at least oneradical initiator (iii) in the at least one methacrylic acid ester (i)equals at least 0.5 weight percent, based on the weight of the at leastone methacrylic acid ester (i). According to an especially preferredembodiment, the radical Initiator (iii) is selected from the groupconsisting of dibenzoyl peroxide and dilauroyl peroxide.

The paste contains 0.01-4 weight percent, preferably 0.01-3 weightpercent, more preferred 0.05-2.5 weight percent, and even more preferred0.05-2 weight percent of at least one radical initiator (iii), based onthe total weight of the paste. Accordingly, the paste can contain one ormore structurally different radical initiators (iii), as long as thetotal weight of the radical initiators (iii) lies in the specifiedrange.

The paste also contains at least one radical initiator (iv) soluble inthe at least one mono-functional, hydrophobic methacrylic acid ester (i)and has no peroxide groups. As used herein, the radical initiator (iv)is understood to be a compound from which a radical can be formed by theaction of the accelerator (v), wherein this radical is capable oftriggering the polymerization of the at least one methacrylic acid ester(i). The radical initiator (iv) thus comprises a radical polymerizationstarter.

In the presence of the accelerator (v), the at least one radicalinitiator (iv) has a decomposition rate that is different from radicalinitiator (iii). According to an especially preferred embodiment, in thepresence of the accelerator (v), the radical initiator (iv) has a higherdecomposition rate than the radical initiator (iii).

According to a preferred embodiment, the solubility of the at least oneradical initiator (iv) in the at least one methacrylic acid ester (i)equals at least 0.5 weight percent, based on the weight of the at leastone methacrylic acid ester (i).

The radical initiator (iv) preferably comprises barbituric acid orbarbituric acid derivatives in which the barbituric acid carries asubstituent on at least one of the positions 1 or 5.

According to the invention, the barbituric acid derivative is preferablymono-substituted. According to a preferred embodiment, a barbituric acidsubstituted at position 5 is used as the radical initiator (iv). Thesubstituent of the barbituric acid derivative furthermore preferablycomprises a hydrophobic substituent. Preferably, the barbituric acidderivative comprises an alkyl, cycloalkyl, or aryl derivative of thebarbituric acid.

According to an especially preferred embodiment, the barbituric acidderivative is selected from the group consisting of cyclohexylbarbituric acid, 1,3,5-trimethyl barbituric acid, 1-phenyl-5-benzylbarbituric acid, 1-benzyl-5-phenyl barbituric acid, 1,3-dimethylbarbituric acid, 1,3-dimethyl-5-phenyl barbituric acid,1-cyclohexyl-5-ethyl barbituric acid, 5-lauryl barbituric acid,1-n-butyl-barbituric acid, 5-n-butyl barbituric acid, 5-allyl barbituricacid, 5-hydroxy-5-butyl barbituric acid, 5,5-dibromobarbituric acid,trichlorobarbituric acid, 5-nitrobarbituric acid, 5-aminobarbituricacid, 5-hydroxy barbituric acid, and 5,5-dihydroxy barbituric acid.

In one very especially preferred embodiment, the barbituric acidderivative is selected from the group consisting of1-cyclohexyl-5-ethyl-barbituric acid, 1-n-butyl-barbituric acid, and5-n-butyl-barbituric acid.

According to the invention, the term “barbituric acid derivatives” alsoincludes alkaline earth salts and alkali salts of these barbituric acidderivatives.

The paste contains 0.01-4 weight percent, preferably 0.01-3 weightpercent, more preferred 0.05-2.5 weight percent, and even more preferred0.05-2 weight percent of at least one radical initiator (iv), based onthe total weight of the paste. Accordingly, the paste can contain one ormore structurally different radical initiators (iv), as long as thetotal weight of the radical initiator (iv) lies in the specified range.

The paste further contains at least one accelerator (v) soluble in theat least one methacrylic acid ester (i) and is capable of formingradicals from the radical initiators (iii) and (iv).

According to a preferred embodiment, the solubility of the accelerator(v) in the at least one methacrylic acid ester (i) equals at least 0.5weight percent, based on the weight of the at least one methacrylic acidester (i).

Accelerators that are capable of forming radicals from the radicalinitiators (iii) and (iv) are understood to be compounds that canconvert the radical initiators (iii) and (iv) into radicals, optionallyin the presence of additional compounds contained in the paste accordingto the invention, as for example halide ions. Such accelerators are wellknown from the prior art.

The accelerator (v) preferably comprises a salt having ions of metalsthat can assume, besides the oxidation stage 0, at least two additionaloxidation stages. According to an especially preferred embodiment, themetal ions are selected from the group consisting of copper ions, ironions, cobalt ions, and manganese ions. Accordingly, preferably an ironsalt, a cobalt salt, or a manganese salt is used as the accelerator (v).According to a very especially preferred embodiment, the accelerator (v)is selected from the group consisting of copper(II)-2-ethylhexanoate,copper(II)-laurate, copper(II)-decanoate, copper(II)-octoate, copper(II)acetylacetonate, and copper(II)-methacrylate.

The paste contains 0.00001-4 weight percent, preferably 0.0001-3 weightpercent, more preferred 0.001-3 weight percent, and even more preferred0.05-2 weight percent of at least one accelerator (v), based on thetotal weight of the paste. Accordingly, the paste can contain one ormore structurally different accelerators (v), as long as the totalweight of the accelerator (v) lies in the specified range.

The paste also contains at least one halide salt (vi). The halide salt(vi) preferably comprises a halide salt soluble in the at least onemethacrylic acid ester (i). According to a preferred embodiment, thesolubility of the halide salt (vi) in the at least one methacrylic acidester (i) equals at least 0.5 weight percent, based on the weight of theat least one methacrylic acid ester (i).

According to the invention, halide salts (vi) are understood to be saltsthat contain at least one type of halide ions and dissociate in the atleast one methacrylic acid ester (i). Preferably, the halide ionscomprise chloride ions or bromide ions, very preferred chloride ions.According to the invention, preferably metal halides, hydrochlorides,and quaternary ammonium halide salts can be used as the halide salts.

According to an especially preferred embodiment, the halide salt (vi) isselected from the group consisting of copper(II)-chloride,copper(II)-bromide, iron(III)-chloride, iron(III)-bromide,cobalt(II)-chloride, cobalt(II)-bromide, triethylamine hydrochloride,triethylamine hydrobromide, propylamine hydrochloride, butylaminehydrochloride, methacryloyl choline chloride, methyltrioctylammoniumchloride, and triethyl benzyl ammonium chloride.

The percentage of the at least one halide salt (vi) equals 0.001-5weight percent, preferably 0.005-4 weight percent, and more preferred0.01-3 weight percent, based on the total weight of the paste.Accordingly, the paste can contain one or more structurally differenthalide salts (vi), as long as the total weight of the halide salts (vi)lies in the specified range.

The paste also contains at least one cross-linking agent (vii). As usedherein, the cross-linking agent is understood to be a multi-functionalcompound capable of entering into covalent bonds with at least twomonomer units that are different from each other. The cross-linkingagent (vii) comprises a bi-functional or tri-functional compound.According to the invention the cross-linking agent should causecross-linking of the polymerizing, mono-functional, hydrophobicmethacrylic acid ester during the curing of the bone cement.

According to a preferred embodiment, the cross-linking agent (vii) hasat least two acrylate groups. Especially preferred, the cross-linkingagent (vii) is selected from the group consisting of ethylene glycoldimethacrylate, butylene glycol dimethacrylate (e.g.,butane-1,4-diol-dimethacrylate) and hexamethylene dimethacrylate (e.g.,hexane-1,6-diol-dimethacrylate).

The percentage of the at least one cross-linking agent (vii) equals0.2-3 weight percent, preferably 0.5-2.75 weight percent, and morepreferred 1-2.5 weight percent, based on the total weight of the paste.Accordingly, the paste can contain one or more structurally differentcross-linking agents (vii), as long as the total weight of thecross-linking agents (vii) lies in the specified range.

In addition, the paste can also contain further components. Thesecomponents can be selected, for example, from the group consisting ofpharmaceutically active substances, radiopaque materials, dyes, andstabilizers. According to preferred embodiments, these comprise thosepharmaceutically active substances, radiopaque materials, dyes, and/orstabilizers that were described above in connection with the kit.

The kit according to the invention or the paste according to theinvention can preferably be used for fixing joint endoprostheses. Forthis purpose, preferably a paste is produced from the kit according tothe invention and this is used analogously to the pastes known from theprior art for fixing joint endoprostheses.

Furthermore, the kit according to the invention or the paste accordingto the invention can also be used for filling bone defects. For thispurpose, a paste is likewise preferably produced from the kit accordingto the invention and this is used analogously to the pastes known fromthe prior art for filling bone defects.

EMBODIMENT EXAMPLES

The monomers and the other chemicals used in Examples 1-3 were providedin pa. purity and were procured from the wholesale chemical trade.

Poly(methyl methacrylate)-co-methyl acrylate having a molecular weightof approximately 200,000 g/mol was used. This polymer is designatedbelow for simplicity as PMMA. In addition, a poly(methyl methacrylate)cross-linked with ethylene glycol dimethacrylate was used, which isdesignated below as cross-linked PMMA. Aliquat 336 stands formethyltrioctylammonium chloride below.

The respective pastes of the kit components (a), (b), and (c) wereproduced, in a manner as follows: First, the methyl methacrylate wasweighed in an inert plastic vessel. Then, the stabilizer and therespective initiator, or in (c) the accelerator, were dissolved in themethyl methacrylate while stirring at room temperature. Next, all of theother components were added. The resulting mixtures were thenintensively mixed. Brushable pastes were thus formed.

Example 1 Kit 1

Methacrylic acid- Radical Initiator/ Compositions ester FillersAccelerator Stabilizer Kit Component 16.2 g Methyl 4.0 g Zirconium 0.8 gDibenzoyl 20 mg 2,6-Di-tert- (a1) methacrylate; dioxide; peroxide (75%)butyl phenol 0.6 g Ethylene 8.8 g PMMA; glycol 9.2 g cross-linkeddimethacrylate PMMA; 0.4 g Methacrylamide Kit Component 16.2 g Methyl4.0 g Zirconium 2.4 g 1- 20 mg 2,6-Di-tert- (b1) methacrylate, dioxide;Cyclohexyl-5- butyl phenol 0.6 g Ethylene 8.8 g PMMA; ethyl-barbituricglycol 7.6 g cross-linked acid; dimethacrylate PMMA; 0.4 g 50 mg AliquatMethacrylamide 336 Kit Component 16.2 g Methyl 4.6 g Zirconium 3 mgCopper(II)- 20 mg 2,6-Di-tert- (c1) methacrylate, dioxide;2-ethylhexanoate butyl phenol 0.6 g Ethylene 8.6 g PMMA; glycol 9.6 gcross-linked dimethacrylate PMMA; 0.4 g Methacrylamide

The kit components a1, b1, and c1 were mixed with each otherintensively. A brushable cement paste was produced, which could beworked up to ca. 4 minutes and was cured after ca. 6 minutes. The curedcement was a white solid body.

Example 2 Kit 2

Methacrylic acid- Radical Initiator/ Compositions ester FillersAccelerator Stabilizer Kit Component 16.2 g Methyl 4.0 g Zirconium 0.8 gDibenzoyl 20 mg 2,6-Di-tert- (a2) methacrylate; dioxide; peroxide (75%)butyl phenol 0.6 g Ethylene 8.8 g PMMA; glycol 9.2 g cross-linkeddimethacrylate PMMA; 0.4 g Methacrylamide Kit Component 16.2 g Methyl4.0 g Zirconium 2.4 g 1- 20 mg 2,6-Di-tert- (b2) methacrylate, dioxide;Cyclohexyl-5- butyl phenol 0.6 g Ethylene 8.8 g PMMA; ethyl-barbituricglycol 5.9 g cross-linked acid; dimethacrylate PMMA; 0.4 gMethacrylamide; 1.7 g Gentamicin sulfate (AK 610) Kit Component 16.2 gMethyl 4.6 g Zirconium 3 mg Copper(II)- 20 mg 2,6-Di-tert- (c2)methacrylate, dioxide; 2- butyl phenol 0.6 g Ethylene 8.8 g PMMA;ethylhexanoate; glycol 9.4 g cross-linked 50 mg Aliquat dimethacrylatePMMA; 0.4 g 336, 10 mg 2- Methacrylamide Ethylhexanoic acid

The kit components a2, b2, and c2 were mixed with each otherintensively. A brushable cement paste was produced, which could beworked for up to ca. 4 minutes and was cured after ca. 6 minutes. Thecured cement was a white solid body.

With the kits of Examples 1 and 2, sample cement bodies (strips) withthe dimensions 75 mm×10 mm×3.3 mm were produced. For determining theflexural strength and the impact strength (Dynstat method), samplecement bodies with dimensions 16 mm×10 mm×3.3 mm were produced. Thesesample bodies were stored 24 hours at 23° C. In addition, test bodieswere stored in water for 24 hours at 37° C.

The 4-point flexural strength and the flexural modulus of the storedsample bodies were determined with the help of a Zwick universal testingmachine.

4-Point Flexural Strength Flexural Strength Flexural Modulus ExamplesStorage Conditions [MPa] [MPa] Kit 1 Air/23° C./24 hr 58.2 ± 0.7 2374 ±22 Kit 1 Water/37° C./24 hr 72.8 ± 1.6 2632 ± 28 Kit 2 Air/23° C./24 hr57.2 ± 0.8 2250 ± 48 Kit 2 Water/37° C./24 hr 59.8 ± 3.8 2286 ± 23

The flexural strength and the impact strength were determined with aDynstat test apparatus.

Flexural Strength Impact Example Storage Conditions [MPa] Strength[kJ/m2] Kit 1 Air/23° C./24 hr 89.6 ± 1.8 4.91 ± 0.27 Kit 1 Water/37°C./24 hr 110.3 ± 2.7  4.49 ± 0.13 Kit 2 Air/23° C./24 hr 76.8 ± 1.0 2.78± 0.08 Kit 2 Water/37° C./24 hr 72.5 ± 1.1 2.58 ± 0.27

Example 3

The kit components described below were produced analogously to thepreceding examples.

Kit Component (a)

Methacrylic acid- Compositions ester Fillers Radical InitiatorStabilizer A1 16.0 g Methyl 4.0 g Zirconium 0.9 g Dibenzoyl 20 mg 2,6-methacrylate, dioxide; peroxide (75%) Di-tert-butyl 0.4 g Ethylene 11.0g PMMA; phenol glycol 7.7 g cross-linked dimethacrylate PMMA; A2 16.0 gMethyl 4.0 g Zirconium 0.9 g Dibenzoyl 20 mg 2,6- methacrylate, dioxide;peroxide (75%) Di-tert-butyl 0.4 g Butane-1,4- 11.0 g PMMA; phenoldiol-dimethacrylate 7.7 g cross-linked PMMA; A3 16.0 g Methyl 4.0 gZirconium 0.9 g Dibenzoyl 20 mg 2,6- methacrylate, dioxide; peroxide(75%) Di-tert-butyl 0.4 g Hexane-1,6- 11.0 g PMMA; phenol dimethacrylate6.2 g cross-linked PMMA; A4 16.0 g Methyl 4.0 g Zirconium 0.9 gDibenzoyl 40 mg 2,6- methacrylate, dioxide; peroxide (75%) Di-tert-butyl0.4 g Ethylene 11.0 g PMMA; phenol glycol 6.2 g cross-linkeddimethacrylate PMMA; A5 16.0 g Methyl 4.0 g Zirconium 0.9 g Dibenzoyl 40mg 2,6- methacrylate, dioxide; peroxide (75%) Di-tert-butyl 0.4 gButane-1,4- 11.0 g PMMA; phenol diol-dimethacrylate 6.2 g cross-linkedPMMA; A6 16.0 g Methyl 4.0 g Zirconium 0.9 g Dibenzoyl 60 mg 2,6-methacrylate, dioxide; peroxide (75%) Di-tert-butyl 0.4 g Hexane-1,6-11.0 g PMMA; phenol dimethacrylate 6.2 g cross-linked PMMA; A7 16.0 gMethyl 4.0 g Zirconium 0.8 g Dilauroly 20 mg 2,6- methacrylate, dioxide;peroxide Di-tert-butyl 0.4 g Ethylene 11.0 g PMMA; phenol glycol 7.8 gcross-linked dimethacrylate PMMA; A8 14.0 g Methyl 4.0 g Zirconium 0.8 gDilauroly 20 mg 2,6- methacrylate, dioxide; peroxide Di-tert-butyl 0.4 gEthylene 11.0 g PMMA; phenol glycol 7.8 g cross-linked dimethacrylatePMMA; A9 16.0 g Methyl 16.0 g Zirconium 0.8 g Dilauroly 20 mg 2,6-methacrylate, dioxide; peroxide Di-tert-butyl 0.4 g Hexane-1,6- 6.8 gPMMA; phenol dimethacrylate A10 16.0 g Methyl 4.0 g Barium 0.9 gDibenzoyl 20 mg 2,6- methacrylate, sulfate; peroxide Di-tert-butyl 0.4 gEthylene 11.0 g PMMA; phenol glycol 7.7 g cross-linked dimethacrylatePMMA; A11 16.0 g Methyl 6.0 g Calcium 0.9 g Dibenzoyl 20 mg 2,6-methacrylate, carbonate; peroxide Di-tert-butyl 0.4 g Ethylene 11.0 gPMMA; phenol glycol 5.7 g cross-linked dimethacrylate PMMA A12 16.0 gMethyl 4.0 g Tantalum 0.9 g Dibenzoyl 20 mg 2,6- methacrylate, powder;peroxide Di-tert-butyl 0.4 g Hexane-1,6- 11.0 g PMMA; phenoldimethacrylate 7.7 g cross-linked PMMA;

Kit Components (b)

Methacrylic acid- Compositions ester Fillers Radical InitiatorStabilizer B1 16.0 g Methyl 4.0 g Zirconium 2.4 g 1- 20 mg 2,6-Di-methacrylate, dioxide; Cyclohexyl-5-ethyl tert-butyl 0.4 g Ethylene 11.0g PMMA; barbituric acid; phenol glycol 6.2 g cross-linked 60 mg Aliquat336 dimethacrylate PMMA; B2 16.0 g Methyl 4.0 g Zirconium 2.4 g 1- 20 mg2,6-Di- methacrylate, dioxide; Cyclohexyl-5-ethyl tert-butyl 0.4 gButane-1,4- 11.0 g PMMA; barbituric acid; phenol diol-dimethacrylate 6.2g cross-linked 60 mg Aliquat 336 PMMA; B3 16.0 g Methyl 4.0 g Zirconium2.4 g 1- 20 mg 2,6-Di- methacrylate, dioxide; Cyclohexyl-5-ethyltert-butyl 0.4 g Hexane-1,6- 11.0 g PMMA; barbituric acid; phenoldimethacrylate 6.2 g cross-linked 60 mg Aliquat 336 PMMA; B4 16.0 gMethyl 4.0 g Zirconium 2.4 g 1- 40 mg 2,6-Di- methacrylate, dioxide;Cyclohexyl-5-ethyl tert-butyl 0.4 g Ethylene 11.0 g PMMA; barbituricacid; phenol glycol 6.2 g cross-linked 60 mg Aliquat 336 dimethacrylatePMMA; B5 16.0 g Methyl 4.0 g Zirconium 2.4 g 1- 40 mg 2,6-Di-methacrylate, dioxide; Cyclohexyl-5-ethyl tert-butyl 0.4 g Butane-1,4-11.0 g PMMA; barbituric acid; phenol diol-dimethacrylate 6.2 gcross-linked 60 mg Aliquat 336 PMMA; B6 16.0 g Methyl 4.0 g Zirconium2.4 g 1- 60 mg 2,6-Di- methacrylate, dioxide; Cyclohexyl-5-ethyltert-butyl 0.4 g Hexane-1,6- 11.0 g PMMA; barbituric acid; phenoldimethacrylate 6.2 g cross-linked 60 mg Aliquat 336 PMMA; B7 16.0 gMethyl 4.0 g Zirconium 2.4 g 1-n-Butyl-5- 20 mg 2,6- methacrylate,dioxide; n-butyl-barbituric Di-tert-butyl 0.4 g Ethylene 11.0 g PMMA;acid; phenol glycol 6.2 g cross-linked 60 mg Aliquat 336 dimethacrylatePMMA; B8 14.0 g Methyl 4.0 g Zirconium 2.4 g 1- 20 mg 2,6- methacrylate,dioxide; Cyclohexyl-5-ethyl Di-tert-butyl 0.4 g Ethylene 11.0 g PMMA;barbituric acid; phenol glycol 8.2 g cross-linked 60 mg Aliquat 336dimethacrylate PMMA; B9 16.0 g Methyl 16.0 g Zirconium 2.4 g 1- 20 mg2,6- methacrylate, dioxide; Cyclohexyl-5-ethyl Di-tert-butyl 0.4 gHexane-1,6- 5.2 g PMMA; barbituric acid; phenol dimethacrylate 60 mgAliquat 336 B10 16.0 g Methyl 4.0 g Barium 2.4 g 1-n-Butyl-5- 20 mg 2,6-methacrylate, sulfate; n-butyl-barbituric Di-tert-butyl 0.4 g Ethylene11.0 g PMMA; acid; phenol glycol 6.2 g cross-linked 60 mg Aliquat 336dimethacrylate PMMA; B11 16.0 g Methyl 6.0 g Calcium 2.4 g 1-n-butyl-5-20 mg 2,6- methacrylate, carbonate; n-butyl-barbituric Di-tert-butyl 0.4g Ethylene 11.0 g PMMA; acid; phenol glycol 4.2 g cross-linked 60 mgAliquat 336 dimethacrylate PMMA; B12 16.0 g Methyl 4.0 g Tantalum 2.4 g1- 60 mg 2,6- methacrylate, powder; Cyclohexyl-5-ethyl Di-tert-butyl 0.4g Hexane-1,6- 11.0 g PMMA; barbituric acid; phenol dimethacrylate 6.2 gcross-linked 60 mg Aliquat 336 PMMA; B13 16.0 g Methyl 4.0 g Zirconium2.4 g 1-Cyclohexyl-5- 20 mg 2,6- methacrylate, dioxide; ethyl barbituricacid; Di-tert- 0.4 g Ethylene 11.0 g PMMA; 60 mg Aliquat 336 butylglycol 4.6 g cross-linked phenol dimethacrylate PMMA; 1.6 g Gentamicinsulfate B14 14.0 g Methyl 4.0 g Zirconium 2.4 g 1-Cyclohexyl-5- 20 mg2,6- methacrylate, dioxide; ethyl barbituric acid; Di-tert- 0.4 gEthylene 11.0 g PMMA; 60 mg Aliquat 336 butyl glycol 8.2 g cross-linkedphenol dimethacrylate PMMA; 5 mg Lissamine green, 5 mg 2- Ethyl-hexanoicacid B15 14.0 g Methyl 4.0 g Zirconium 2.4 g 1-Cyclohexyl-5- 20 mg 2,6-methacrylate, dioxide; ethyl barbituric acid; Di-tert- 0.4 g Ethylene11.0 g PMMA; 60 mg Tetrabutyl butyl glycol 8.2 g cross-linked ammoniumchloride phenol dimethacrylate PMMA; 5 mg Lissamine green, 5 mg 2-Ethyl-hexanoic acid

Kit Components (c)

Methacrylic acid- Compositions ester Fillers Stabilizer Accelerator C116.0 g Methyl 4.0 g Zirconium 3 mg Copper(II)-2- 20 mg 2,6-methacrylate, dioxide; ethylhexanoate Di-tert-butyl 0.4 g Ethylene 11.0g PMMA; phenol glycol 8.6 g cross-linked dimethacrylate PMMA; C2 16.0 gMethyl 4.0 g Zirconium 3 mg Copper(II)-2- 20 mg 2,6- methacrylate,dioxide; ethylhexanoate Di-tert-butyl 0.4 g Butane-1,4- 11.0 g PMMA;phenol diol-dimethacrylate 8.6 g cross-linked PMMA; C3 16.0 g Methyl 4.0g Zirconium 3 mg Copper(II)-2- 20 mg 2,6- methacrylate, dioxide;ethylhexanoate Di-tert-butyl 0.4 g Hexane-1,6- 11.0 g PMMA; phenoldimethacrylate 8.6 g cross-linked PMMA; C4 16.0 g Methyl 4.0 g Zirconium2 mg Copper(II)- 40 mg 2,6- methacrylate, dioxide; methacrylateDi-tert-butyl 0.4 g Ethylene 11.0 g PMMA; phenol glycol 8.6 gcross-linked dimethacrylate PMMA; C5 16.0 g Methyl 4.0 g Zirconium 2 mgCopper(II)- 40 mg 2,6- methacrylate, dioxide; methacrylate Di-tert-butyl0.4 g Butane-1,4- 11.0 g PMMA; phenol diol-dimethacrylate 8.6 gcross-linked PMMA; C6 16.0 g Methyl 4.0 g Zirconium 2 mg Copper(II)- 60mg 2,6- methacrylate, dioxide; methacrylate Di-tert-butyl 0.4 gHexane-1,6- 11.0 g PMMA; phenol dimethacrylate 8.6 g cross-linked PMMA;Radical Initiator C7 16.0 g Methyl 4.0 g Zirconium 2 mg Copper(II)- 20mg 2,6- methacrylate, dioxide; acetylacetonate Di-tert-butyl 0.4 gEthylene 11.0 g PMMA; phenol glycol 8.6 g cross-linked dimethacrylatePMMA; C8 14.0 g Methyl 6.0 g Zirconium 2 mg Copper(II)- 20 mg 2,6-methacrylate, dioxide; acetylacetonate Di-tert-butyl 0.4 g Ethylene 11.0g PMMA; phenol glycol 8.6 g cross-linked dimethacrylate PMMA; C9 16.0 gMethyl 16.0 g Zirconium 2 mg Copper(II)- 20 mg 2,6- methacrylate,dioxide; acetylacetonate Di-tert-butyl 0.4 g Hexane-1,6- 7.6 g PMMA;phenol dimethacrylate C10 16.0 g Methyl 4.0 g Barium 3 mg Copper(II)- 20mg 2,6- methacrylate, sulfate; 2-ethylhexanoate Di-tert-butyl 0.4 gEthylene 11.0 g PMMA; phenol glycol 8.6 g cross-linked dimethacrylatePMMA; C11 16.0 g Methyl 6.0 g Calcium 3 mg Copper(II)- 20 mg 2,6-methacrylate, carbonate; 2-ethylhexanoate Di-tert-butyl 0.4 g Ethylene11.0 g PMMA; phenol glycol 6.6 g cross-linked dimethacrylate PMMA C1216.0 g Methyl 4.0 g Tantalum 3 mg Copper(II)- 20 mg 2,6- methacrylate,powder; 2-ethylhexanoate Di-tert-butyl 0.4 g Hexane-1,6- 11.0 g PMMA;phenol dimethacrylate 8.6 g cross-linked PMMA;

It will be appreciated by those skilled in the art that changes could bemade to the embodiments described above without departing from the broadinventive concept thereof. It is understood, therefore, that thisinvention is not limited to the particular embodiments disclosed, but itis intended to cover modifications within the spirit and scope of thepresent invention as defined by the appended claims.

We claim:
 1. A paste comprising: (i) 15-50 weight percent of at leastone mono-functional, hydrophobic methacrylic acid ester, (ii) 40-85weight percent of at least one filler, (iii) 0.01-4 weight percent of atleast one radical initiator soluble in the methacrylic acid ester (i)and having at least one peroxide group, (iv) 0.01-4 weight percent of atleast one radical initiator soluble in the methacrylic acid ester (i)and having no peroxide groups, (v) 0.000001-3 weight percent of at leastone accelerator soluble in the methacrylic acid ester (i) and capable offorming radicals from the radical initiators according to (iii) and(iv), wherein the at least one accelerator is selected from the groupconsisting of copper(II)-2-ethylhexanoate, copper(II)-laurate,copper(II)-decanoate, copper(II)-octoate, copper(II)-acetylacetonate,and copper(II)-methacrylate, (vi) 0.001-5 weight percent of at least onehalide salt, and (vii) 0.2-3 weight percent of at least onecross-linking agent.
 2. A method for fixing joint endoprostheses orfilling bone defects, the method comprising applying the paste accordingto claim 1.